PRIMARY OBJECTIVETo evaluate the safety and tolerability of single ascending, intravenous doses of ACT017 administered as a 6-hour intravenous (i.v.) infusionSECONDARY OBJECTIVES* To evaluate the pharmacokinetics of single ascending, intravenous…
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety
* Adverse Events (AEs)
* Clinical laboratory results
* Electrocardiogram (ECG)
* Vital signs
* Coagulation parameters (PT, PTT, INR)
* Platelet count
* GPVI expression
* Immunogenicity / anti-drug antibodies (ADA)
Secondary outcome
Pharmacokinetics
Pharmacokinetic parameters will be derived by non-compartmental analysis of the
platelet free plasma concentration-time profiles. Details will be specified in
the pharmacokinetics (PK) analytical plan.
Pharmacodynamics
* Bleeding time
* Collagen-induced platelet aggregation
Background summary
Blood platelets are critically involved in cardiovascular diseases including
stroke. This is why antiplatelet agents are in first line of therapy and
secondary prevention in coronary artery diseases. The use of antiplatelet
agents is also suitable to treat stroke and prevent recurrence but the
currently available molecules are not recommended at the acute phase (0 to 12
hours) due to the associated risk of hemorrhagic transformation. Early
administration of intravenous aspirin in patients with acute ischemic stroke
treated with rtPA is associated with increased of intracranial hemorrhage.
Therefore, there is still a need for a safe and efficient antithrombotic agent
administrable at the acute phase without inducing a bleeding risk in order to
reduce the size of the clot, to favor cerebral reperfusion and to prevent
recurrences.
Study objective
PRIMARY OBJECTIVE
To evaluate the safety and tolerability of single ascending, intravenous doses
of ACT017 administered as a 6-hour intravenous (i.v.) infusion
SECONDARY OBJECTIVES
* To evaluate the pharmacokinetics of single ascending, intravenous doses of
ACT017 administered as a 6-hour i.v. infusion
* To evaluate the pharmacodynamics (i.e. inhibition of platelet aggregation and
absence of an effect on bleeding time) of single ascending, intravenous doses
of ACT017 administered as a 6-hour i.v. infusion
Study design
Single-center, Phase I, single ascending dose (SAD) study with a randomized,
double-blind, placebo-controlled design in 6 treatment groups of 8 subjects (6
active; 2 placebo), in which treatments are given as a 6-hour i.v. infusion.
Intervention
Screening
This includes an evaluation of the inclusion and exclusion criteria to check
for eligibility. This evaluation will be performed within 2 to 28 days before
study drug administration.
In-clinic period
After a re-evaluation of the inclusion and exclusion criteria on Day -1,
eligible subjects will enter the in-clinic phase and leave on the morning of
Day 3 after all study related procedures and approval by the Investigator. On
Day 1, the study drug will be given once as an infusion of 6 hours. During this
in-clinic phase, documentation of AEs will be done, in combination with blood
sampling for pharmacokinetics (PK), blood sampling for pharmacodynamics (PD),
clinical laboratory tests, urine collection, physical examination, weight,
vital signs, and ECG.
Follow-up
Follow-up will take place on Day 7 ±2 days. During this visit, documentation of
AEs will be done, in combination with vital signs, physical examination
(including weight), blood sampling for PD, clinical laboratory tests, and ECG.
Study burden and risks
The study drug ACT017 has not been administered to humans before. ACT has been
administered to animals, as required by regulatory (health) authorities. The
dose has been selected based on the results of animal testing. The health risks
are limited at these dose levels. Disadvantages of participation in the study
may be the possible discomforts of the measurements performed in the study and
the possible occurrence of side effects.
The blood collection procedure is not dangerous, but may cause discomfort or
bruising. Occasionally, fainting, bleeding or an infection at the blood
sampling site can occur.
One of the methods evaluating the clot properties of your blood uses a device
making a small cut in your skin. These cuts may possibly result in small scars.
The healthy volunteers will not personally benefit from participation in this
study, but participation may contribute to further developments in treating
brain infarction.
Hôpital Bichat, Bâtiment Inserm U1148 46 rue Henri Huchard
Paris Cedex 18 75018
FR
Hôpital Bichat, Bâtiment Inserm U1148 46 rue Henri Huchard
Paris Cedex 18 75018
FR
Listed location countries
Age
Inclusion criteria
1. Males or non-pregnant, non-breastfeeding females, aged *18 and 65 years. Female subjects must be of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation, hysterectomy or bilateral oophorectomy; or as post-menopausal females defined as 12 months amenorrhea and follicle stimulating hormone (FSH) levels >40 IU/L.
2. Body mass index (BMI) *18 kg/m2 and 30 kg/m2 at screening.
3. A resting pulse *40 beats per minute (bpm) and *100 bpm at screening and on Day -1.
4. A resting systolic blood pressure of *150 mmHg and a resting diastolic blood pressure of *95 mmHg at screening and on Day -1.
5. Baseline laboratory test values within reference ranges based on the blood and urine samples taken at screening and on Day -1. Out of normal ranges values may be accepted by the Investigator, if not clinically significant. Values for hemostasis and coagulation blood test, for bleeding time and platelet aggregation should be normal.
Exclusion criteria
1. The subject has a history of hemorrhagic disease or venous or arterial thrombotic disease.
2. The subject has a history or presence of any disorder with an increased risk of bleeding (e.g. ulcus pepticus, hemorrhoids).
3. The subject has used drugs modifying hemostasis or platelet function within the last month prior to administration of the study drug (i.e. aspirin, antiplatelet drugs, anti-vitamin K drugs and anticoagulant drugs).
4. The subject has used anti-histamines within the last month prior to administration of the study drug.
5. The subject has taken prescription or non-prescription medication, herbal remedies, vitamins or minerals within 2 weeks prior to administration of the study drug (or within 5 half-lives prior to administration of the study drug for any medication ingested, whichever is longer).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-003047-38-NL |
| CCMO | NL63251.056.17 |